“We might 'turn a knob' but we can't predict what will happen”

Markus Jeschek is a tenure-track assistant professor at EPFL's Schools of Life Sciences and Basic Sciences. He leads the Lonza Chair in Sustainable Biosynthesis, where he and his team aim to build microbes with new capabilities.

What do you research?

Our overarching goal is to build synthetic microbes that fulfil different needs of daily life. Microbes have a versatile metabolism that allows them to grow on renewable or even waste materials. If you apply the right tricks, they can convert them even into industrially useful chemicals. Or take our gut: the microbial community there can sense different stimuli and in response influence the chemical conditions, which impacts our well-being.

We build on these remarkable capabilities and expand them through genetic modifications. The aim is to equip microbes with entirely new functions – for example, to produce novel chemical products, sense new stimuli, or respond in different and controllable ways.

What led you to this field?

In a biology class in school, we learned that bacteria use small, ring-shaped DNA molecules, called plasmids, to exchange genetic information. What fascinated me is that you can replace that information with whatever you want, for example with the human insulin gene. The bacteria will then produce the antidiabetic hormone, which is done at hundred-thousand-liter scale to make human-identical insulin at low cost and high consistency. Even though this is an old example, the fact that such things are possible with relatively simple tricks still fascinates me.

What fascinates you about your topic?

Our society relies heavily on petrochemicals. It’s hard to find an object that hasn’t been made or treated with them. These chemicals are produced in vast quantities through hazardous, energy-intensive processes from petroleum. Developing sustainable microbial alternatives to obtain such chemicals is a major motivation for my team and me.

Can bacteria consume plastics and things like that?

Yes, they can. Bacteria are essentially complex reaction networks driven by protein molecules called enzymes. There are enzymes known as PETases—named after the PET plastic we all know—that can chemically degrade plastic. This is an exciting research area.

Other examples include agricultural residues, the material left on fields after harvest. Instead of wasting or burning it, we can use it to produce useful things. For instance, vanillin is a flavor molecule we work with often. Imagine starting from waste and ending with something that smells good and can be added to food.

What challenges do you encounter?

A big challenge is the complexity of microbes. You can think of them as a network of thousands of interacting biomolecules. When we modify their genes to produce something new, we might “turn a knob”, but we can’t predict what will happen. It’s a non-trivial problem.

Therefore, nowadays most engineering is still done via trial and error: we make genetic changes, see what happens, and hope for the best. Sometimes it works; often, it doesn’t. It’s laborious and prone to failure.

Our research aims to make this process more “rational” and thus efficient. We do this by developing molecular tools to test millions of genetic variants for specific traits—say, the ability to produce a chemical. We then use the data, often billions of data points, to train machine learning models that predict how new genetic modifications will affect the desired trait without having to do more experiments. This dramatically increases the chances of success and the speed at which we can develop new bioprocesses.

What are you teaching at EPFL?

I have launched a course in Chemical Biology this fall, aimed at fifth-semester students in chemistry and open to life science students, too. It showcases how we can use chemical tools to better understand and manipulate biological systems—for example, how drugs interact with enzymes or how new diagnostics can be built with chemistry.

Next year, I plan to introduce a specialized course on Synthetic and Applied Microbiology for the late BSc and MSc level. Students will learn about state-of-the-art technologies for the construction of microbial systems with new-to-nature properties and their applications in modern life science.

What do you enjoy about teaching?

If I do my job right, I get to watch students grow significantly in a short time. Within 12 to 14 weeks, they gain the knowledge and confidence to navigate new topics independently and come up with ideas of their own. That’s extremely rewarding.

Personally, I’ve learned best when I was actively engaged. That sense of having achieved something on my own has always been a strong motivator. So, I believe that teaching should go beyond delivering knowledge—it should create a framework that encourages creativity and participation. That’s the kind of program I want to build here.

Tell us something interesting about yourself.

There’s a restaurant in Munich formerly owned by a very good friend of mine, and on the wall is a 34,000-piece puzzle I once completed. I wish I still had that kind of time nowadays, but maybe it is just the type of puzzle that has changed. The funny thing is, one piece is missing, unfortunately. But my friend hung it up anyway. If anyone who reads this finds that puzzle, send me proof and I’ll invite you for a drink!